An alternative approach to (S)- and (R)-2-methylglycidol O-benzyl ether derivatives

Article abstract of DOI:10.1016/S0957-4166(01)00230-0

This report describes the gram scale synthesis of (S)- and (R)-2,2,4-trimethyl-4-(hydroxymethyl)-1,3-dioxolanes using the Sharpless asymmetric dihydroxylation (AD) of the Weinreb amide of 2-methyl-2-propenoic acid. The 2-methylglycerol acetonides resultan

Full text of DOI:10.1016/S0957-4166(01)00230-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1383–1388
An alternative approach to (S)- and (R)-2-methylglycidol
O-benzyl ether derivatives
Alberto Avenoza,a,* Carlos Cativiela,b Jesu´s M. Peregrina,a,* David Sucunzaa and
Mar´ıa M. Zurbanoa
aDepartamento de Qu´ımica, Universidad de La Rioja, Grupo de S´ıntesis Qu´ımica de La Rioja, UA-CSIC, 26006 Logron˜o, Spain
bDepartamento de Qu´ımica Orga´nica, Instituto de Ciencia de Materiales de Arago´n, Universidad de Zaragoza-CSIC,
50009 Zaragoza, Spain
Received 2 May 2001; accepted 18 May 2001
Abstract—This report describes the gram scale synthesis of (S)- and (R)-2,2,4-trimethyl-4-(hydroxymethyl)-1,3-dioxolanes using
the Sharpless asymmetric dihydroxylation (AD) of the Weinreb amide of 2-methyl-2-propenoic acid. The 2-methylglycerol
acetonides resultant from protection of the AD products were used as starting materials in the synthesis of O-benzyl ethers of the
valuable C4-chiral building blocks (S)- and (R)-2-methylglycidol. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
erol analogues,11 several choline analogues,12 some
derivatives of cynchomalthoheptaosa,13 and both enan-
tiomers of frontalin.14 Moreover, both enantiomers of 1
were used to prepare 2,2,4-trimethyl-4-(hydroxy-
methyl)-1,3-dioxolanes (S)- and (R)-2,15 two impor-
tant C4-building blocks, which together with their
derivatives were extensively used in the asymmetric
synthesis of numerous natural products.16
Optically active glycidols and their derivatives are a
class of epoxides with great versatility and importance
in organic synthesis, since the presence of a CH2OR
group allows the introduction of a third potentially
electrophilic centre. As a result of their easy availability
and the broad scope of their synthetically useful reac-
tions, several publications have appeared in the
literature.1
However, only minor attention has been paid to the
enantiomers of 2-methylglycidol (S)- and (R)-1,
although several uses are described. For example, selec-
tive protection or oxidation of (S)- and/or (R)-1 and
ring opening of the oxirane ring followed by functional
group transformations led to the formation of aziridines,2
oxazolines3 or oxazolidines,4 which were used in the
asymmetric synthesis of a variety of a-methyl a-amino
acids. Homochiral 2-methylglycidols were also used in
the preparation of various natural products and their
analogues.5,6 Some examples of compounds synthesised
using these chiral units are (22E,25R)-1a,25,26-trihy-
droxy-D22-vitamin D3,7 (23S,25R)-calcitriol lactone,8
dideoxyribosides,9 analogue inhibitors of carnitine
acetyltransferase,10 a series of 1,25-dihydrocholecalcif-
The first synthesis of enantiomerically pure 1 was
achieved in 1983 using the Sharpless asymmetric epoxi-
dation (AE)17 of 2-methyl-2-propen-1-ol, which
afforded the (R)-enantiomer18 with 94% e.e. in 32%
yield and the (S)-enantiomer19 with 85% e.e. in 78%
yield. It is widely recognised that while AE has great
scope, allylic alcohol substrates such as 2-methyl-2-
propen-1-ol20 are not best suited to the methodology
due to the water solubility of the product 1 and its
sensitivity to nucleophilic opening.21 These difficulties
were reduced by using the modified AE procedure22
combined with a non-aqueous work-up, which allowed
the isolation of (R)-1 in 47% yield and 95% e.e.23 In
spite of this, difficulties were still encountered in the
isolation of 1; therefore, Sharpless et al. developed an
* Corresponding author. Fax: +34 941 299621; e-mail: alberto.
avenoza@dq.unirioja.es
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00230-0

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A. A6enoza et al. / Tetrahedron: Asymmetry 12 (2001) 1383–1388
alternative, which involves the in situ transformation of
the crude AE product to obtain a p-nitrobenzoate ester
(or two sulfonate derivatives).24 More recently, (R)-1
has been prepared by chemoenzymatic reactions with
>99% e.e.25 and by epoxidation of 2-methyl-2-propen-1-
ol in supercritical carbon dioxide using a vanadyl salen
oxo-transfer catalyst, which gave moderate 50% yield
and 75% e.e.26
ether (R)-11. To this end, the acetal protecting groups
were cleaved by treatment of (R)-7 with 2N aqueous
HCl to give the diol (S)-9, which was selectively mesyl-
ated at the primary hydroxyl group, yielding alcohol
(R)-10. Subsequent intramolecular Williamson etherifi-
cation by the action of K2CO3 gave the required oxi-
rane (R)-11 (Scheme 2).
(S)-2-Methylglycidyl benzyl ether (S)-11 was synthe-
sised using the same methodology but instead of start-
ing from (S)-7, we applied a divergent route from (S)-8;
therefore its hydrolysis was carried out with 2N HCl to
give the corresponding diol, which was treated in situ
with benzyl bromide in the presence of NaH and Bu4NI
giving directly (S)-11 (Scheme 2).
(S)- and (R)-2-Methylglycidol O-benzyl derivatives 11
were easily formed by the protection of (S)- or (R)-1 as
their benzyl ethers.9 Recently, (S)- and (R)-11 were
prepared by chemoenzymatic synthesis from deracemi-
sation of ( )-11,15,27 which was obtained by epoxidation
of methallyl alcohol using m-CPBA.28 Other attempts
using the AE or Sharpless asymmetric dihydroxylation
(AD)29 gave less satisfactory results with e.e. of <45%.30
The enantiomeric purity of the 2-methylglycidyl benzyl
ethers, the two 2-methylglycerol acetonides and their
derivatives was established by preparation of the
Mosher esters of alcohols (S)- and (R)-1, which were
Given the importance of both enantiomers of 1 and 2
(and their derivatives 7, 8 and 11), and the fact that
(S)-1 and (R)-1 are not commercially available, we
herein report a new straightforward synthetic procedure
for the aforementioned C4-chiral building blocks.
2. Results and discussion
In order to obtain the required C4-building block,
2-methylglycerol acetonide (R)-2 and its benzyl and
methanesulfonyl derivatives, we decided to start our
synthesis from the easily available olefin 3,31 which was
subjected to AD in the presence of AD-mix b to give
the diol (S)-4 (81% yield, 93% e.e.), according to the
previous method reported by Sharpless et al.32 The
amide group of diol (S)-4 was hydrolysed using LiOH
in MeOH at room temperature and the corresponding
carboxylic acid group was esterified with AcCl in
MeOH at reflux to introduce the methyl ester group,
affording the dihydroxy ester (S)-5.33 The diol function
of (S)-5 was protected using 2,2-dimethoxypropane
(DMP) and p-toluenesulfonic acid (p-TsOH) to give the
acetonide (S)-6. This compound has been previously
prepared in racemic form by Lin et al.34 and in enan-
tiomerically pure form by enantioselective lipase-
catalysed hydrolysis35 of ( )-5 (Scheme 1).
Scheme 1. (i) AD-mix b [for (S)-4] or AD-mix a [for (R)-4],
MeSO2NH2, tBuOH/H2O (1:1), 0°C, 12 h, 81%; (ii) (a)
LiOH·H2O, H2O/MeOH (1:3), rt, 2 h; (b) AcCl, MeOH,
reflux, 12 h, 85%; (iii) DMP, p-TsOH, toluene, reflux, 4 h,
93%; (iv) LiAlH4, THF, rt, 4 h, 90%; (v) BnBr, NaH, Bu4NI,
THF, rt, 92%; (vi) MsCl, DIEA, CH2Cl2, rt, 87%.
Treatment of (S)-6 with LiAlH4 gave the required
alcohol (R)-2 which was transformed into two deriva-
tives, the O-benzyl ether (R)-7 using benzyl bromide in
the presence of NaH and Bu4NI and the O-methanesul-
fonyl (S)-8 by treatment with methanesulfonyl chloride
in di-iso-propylethylamine (DIEA) (the apparent inver-
sion [(S)-6“(R)-2“(S)-8] in the reactions is due to a
switch in the CIP-priority and not a result of inversion
at the stereogenic centre (see Scheme 1)).
(S)-2-Methylglycerol acetonide (S)-2 and its derivatives
(S)-7 and (R)-8 were obtained using the same strategy
described above and also starting from olefin 3, but
using AD-mix a in the AD reaction.
Scheme 2. (i) 2N HCl, THF, rt, 2 h, 95%; (ii) MsCl, DIEA,
CH2Cl2, rt, 93%; (iii) K2CO3, THF, reflux, 79%; (iv) (a) 2N
HCl, rt, 2 h, 87%; (b) BnBr, NaH, Bu4NI, THF, rt, 63%.
The chiral building block (R)-7 was used as the starting
material for the preparation of 2-methylglycidyl benzyl

A. A6enoza et al. / Tetrahedron: Asymmetry 12 (2001) 1383–1388
1385
obtained from the acid hydrolysis of (S)-8 and (R)-8
and subsequent epoxide formation by treatment with
NaH in THF (Scheme 3). Alcohol (S)-1 was coupled
with (R)-(−)-methoxytrifluorophenylacetic acid ((R)-
MTPA) in the presence of DCC and DMAP to give
the Mosher ester 12 according to the literature proto-
col.36 In the same way, a mixture of the alcohols
(S)-1 and (R)-1 (in a ratio of 1:3) was transformed
into Mosher esters 12 and 13, respectively. Analysis of
the NMR spectra of ester 12 showed that the enan-
tiomeric purity of compound (S)-12 was at least 96%
(only one isomer was observed in the 1H and 19F
NMR spectra) (Scheme 3).
(ESI) on a Hewlett–Packard 5989B mass spectrome-
ter.
4.2. Methyl 2,3-dihydroxy-2-methylpropenoates (R)-5
and (S)-5
To a solution of (S)-4 (8.60 g, 52.7 mmol) in H2O/
MeOH (1:3, 120 mL), at rt, was added LiOH·H2O
(11.1 g, 264 mmol) and the mixture stirred for 2 h.
The N,O-dimethylhydroxylamine formed in the reac-
tion and MeOH were removed and the mixture was
acidified with conc. HCl to pH 1–2. After removing
the solvent, the white solid was dissolved in MeOH/
HCl, previously prepared by dropwise addition of
AcCl (30 mL) to pre-cooled MeOH (120 mL) at 0°C,
and the mixture was heated under reflux for 12 h.
The mixture was concentrated and the residue parti-
tioned between H2O (50 mL) and CHCl3/iso-propanol
(3:1, 100 mL). The aqueous layer was successively
washed with CHCl3/iso-propanol (4×100 mL), dried
(Na2SO4), concentrated and the crude product was
purified by column chromatography (hexane/ethyl ace-
tate, 3:7) to give (S)-5 as a colourless oil (5.98 g, 44.6
mmol, 85%). [h]2D5=−1.0 (c 2.66, MeOH). 1H NMR
(CDCl3): l 1.35 (s, 3H, CH3), 3.57 (d, 1H, J=11.2
Hz, CH2), 3.80 (d, 1H, J=11.2 Hz, CH2), 3.81 (s, 3H,
CO2CH3). Anal. calcd for C5H10O4: C, 44.77; H, 7.51.
Found: C, 44.61; H, 7.45%. Spectral data were identi-
cal to those reported in the literature (Ref. 37).
3. Conclusions
In summary, starting from commercially available 2-
methyl-2-propenoic acid, we have developed
a
straightforward gram scale synthetic route to prepare
the valuable 2-methylglycerol acetonide building
blocks, (S)-2 and (R)-2, over five steps in enantiomer-
ically pure form and with an overall yield of 58%.
(R)-2 was used as the starting material in stereodiver-
gent syntheses of the 2-methylglycidol O-benzyl
derivatives (S)-11 (three steps, 48% yield) and (R)-11
(four steps, 64% yield).
4. Experimental
4.1. General
Compound (R)-5 (5.95 g, 85%) was obtained using
the method described for its enantiomer (S)-5, but
starting with (R)-4 (8.62 g, 52.7 mmol). [h]2D5=+0.8 (c
2.66, MeOH). Anal. calcd for C5H10O4: C, 44.77; H,
7.51. Found: C, 44.58; H, 7.48%.
Solvents were purified according to standard proce-
dures. Analytical TLC was performed using Poly-
chrom SI F254 plates. Column chromatography was
1
performed using silica gel 60 (230–400 mesh). H and
4.3. Methyl 2,2,4-trimethyl-1,3-dioxolane-4-carboxylates
(R)-6 and (S)-6
13C NMR spectra were recorded on a Bruker ARX-
300 spectrometer, using CDCl3 with TMS as the
internal standard (chemical shifts are reported in ppm
on the l scale, coupling constants in Hz). Optical
rotations were measured on a Perkin–Elmer 341
polarimeter in a 1 cm cell of 1 mL capacity. Micro-
analyses were carried out on a CE Instruments EA-
1110 analyser and were in good agreement with the
calculated values. IR spectra were recorded on a
Perkin–Elmer FT-IR Spectrum 1000 spectrometer.
Mass spectra were obtained by electrospray ionisation
A solution of compound (S)-5 (1.57 g, 11.7 mmol),
2,2-DMP (6.22 g, 58.5 mmol) and TsOH (45 mg, 0.23
mmol) in toluene (25 mL) was heated under reflux for
2 h and then distilled over 15 min to remove the
MeOH formed. 2,2-DMP (6.22 g, 58.5 mmol) was
added, and the procedure was repeated until TLC
analysis showed no remaining starting material and
clean formation of a single product. The solvent was
removed to give a yellow oil, which was purified by
column chromatography (hexane/ethyl acetate, 9:1) to
give (S)-6 as an oil (1.90 g, 10.9 mmol, 93%). [h]2D5=+
1
4.7 (c 1.22, MeOH). H NMR (CDCl3): l 1.38 (s, 3H,
CH3), 1.39 (s, 3H, CH3), 1.47 (s, 3H, CH3), 3.72 (s,
3H, CO2CH3), 3.74 (d, 1H, J=8.7 Hz, CH2), 4.33 (d,
1H, J=8.7 Hz, CH2). Anal. calcd for C8H14O4: C,
55.16; H, 8.10. Found: C, 55.61; H, 8.45%. Spectral
data were identical to those reported in the literature
(Ref. 34).
Using the method described for its enantiomer (S)-6,
compound (R)-6 (1.81 g, 93%) was obtained from
compound (R)-5 (1.50 g, 11.2 mmol). [h]2D5=−4.4 (c
1.14, MeOH). Anal. calcd for C8H14O4: C, 55.16; H,
8.10. Found: C, 54.90; H, 8.61%.
Scheme 3. (i) (a) 2N HCl, THF, rt, 2 h; (b) NaH, THF, rt,
2 h, 90%; (ii) (R)-MTPA, DCC, DMAP, CH2Cl2, rt, 6 h,
48%.

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A. A6enoza et al. / Tetrahedron: Asymmetry 12 (2001) 1383–1388
4.4. (2,2,4-Trimethyl-1,3-dioxolane-4-yl)methanols (R)-2
and (S)-2
in dry dichloromethane (15 mL), at 0°C, methanesul-
fonyl chloride (0.29 g, 2.46 mmol) was added dropwise,
under an inert atmosphere. The reaction mixture was
stirred at rt for 3 h and then a saturated aqueous
NaHCO3 solution (10 mL) was added. The organic
layer was dried (Na2SO4), concentrated in vacuo and
purified by column chromatography (hexane/ethyl ace-
tate, 7:3) to give (S)-8 as an oil (0.40 g, 1.79 mmol,
87%). [h]2D5=+1.0 (c 1.22, MeOH). 1H NMR (CDCl3): l
1.35 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.40 (s, 3H, CH3),
3.04 (s, 3H, SO2CH3), 3.72 (d, 1H, J=9.0 Hz, CH2),
3.99 (d, 1H, J=9.0 Hz, CH2), 4.05 (m, 2H, CH2); 13C
To a vigorously stirred suspension of LiAlH4 (0.85 g,
22.4 mmol) in THF (10 mL), at 0°C, was added drop-
wise a solution of (S)-6 (1.56 g, 8.96 mmol) in THF (15
mL). After stirring the mixture for 4 h, at rt, the
mixture was cooled and carefully quenched by the
addition of H2O (1 mL), 1N NaOH solution (5.1 mL)
and further H2O (5.1 mL). After stirring at rt for 3 h,
the white precipitate was filtered off and washed thor-
oughly with ethyl acetate. The filtrate was dried
(Na2SO4), concentrated in vacuo and purified by
column chromatography (hexane/ethyl acetate, 7:3) to
give (R)-2 as an oil (1.18 g, 8.06 mmol, 90%). [h]2D5=
NMR (CDCl3):
l 22.0, 26.4, 27.1 (CH3), 37.4
(SO2CH3), 71.1, 72.2 (CH2), 78.8 (C(CH3)O), 110.3
(CO2(CH3)2). ESI+ (m/z)=225. Anal. calcd for
C8H16O5S: C, 42.84; H, 7.19; S, 14.30. Found: C, 42.32;
H, 7.31; S, 14.12%.
1
+5.5 (c 0.78, dichloromethane). H NMR (CDCl3): l
1.25 (s, 3H, CH3), 1.37 (s, 3H, CH3), 1.38 (s, 3H, CH3),
3.41 (d, 1H, J=9.9 Hz, CH2), 3.47 (d, 1H, J=9.9 Hz,
CH2), 3.68 (d, 1H, J=9.0 Hz, CH2), 3.93 (d, 1H, J=9.0
Hz, CH2). Anal. calcd for C7H14O3: C, 57.51; H, 9.65.
Found: C, 57.84; H, 9.21%. Spectral data were identical
to those reported in the literature (Ref. 19).
Using the method described for its enantiomer (S)-8,
compound (R)-8 (0.46 g, 87%) was obtained from
compound (S)-2 (0.35 g, 2.39 mmol). [h]2D5=−1.1 (c
1.19, MeOH). Anal. calcd for C8H16O5S: C, 42.84; H,
7.19; S, 14.30. Found: C, 42.41; H, 7.53; S, 14.61%.
Using the method described for its enantiomer (R)-2,
compound (S)-2 (1.12 g, 90%) was obtained from com-
pound (R)-6 (1.48 g, 8.50 mmol). [h]2D5=−5.9 (c 1.29,
dichloromethane). Anal. calcd for C7H14O3: C, 57.51;
H, 9.65. Found: C, 57.12; H, 9.09%.
4.7. 3-Benzyloxy-2-methylpropane-1,2-diol (S)-9
To a solution of (R)-7 (1.60 g, 7.20 mmol) in THF (10
mL), at rt, 2N HCl (10 mL) was added. After stirring
for 2 h, the mixture was extracted with ethyl acetate (20
mL). The organic phase was dried (Na2SO4), concen-
trated in vacuo and purified by column chromatogra-
phy (hexane/ethyl acetate, 6:4) to give (S)-9 as an oil
(1.25 g, 6.86 mmol, 95%). [h]2D5=+6.8 (c 1.05,
dichloromethane). 1H NMR (CDCl3): l 1.14 (s, 3H,
CH3), 3.52 (m, 4H, 2CH2), 4.54 (m, 2H, CH2Ph), 7.32
(m, 5H, Ph). Anal. calcd for C11H16O3: C, 67.32; H,
8.22. Found: C, 67.61; H, 8.45%. Spectral data were
identical to those reported in the literature (Ref. 23).
4.5. 4-Benzyloxymethyl-2,2,4-trimethyl-1,3-dioxolanes
(R)-7 and (S)-7
Alcohol (R)-2 (1.29 g, 8.82 mmol) was dissolved in
THF (25 mL) and the resultant solution was added to
NaH (0.39 g, 9.71 mmol) at 0°C, under an inert atmo-
sphere. The reaction was warmed to rt and BnBr (1.85
g, 10.6 mmol) and Bu4NI (1.00 g, 2.62 mmol) were
added to the mixture. After stirring for 18 h, the
reaction was quenched by the addition of H2O (15 mL)
and extracted with ethyl acetate (25 mL). The organic
extract was dried (Na2SO4), concentrated in vacuo and
purified by column chromatography (hexane/ethyl ace-
tate, 9.5:0.5) to give (R)-7 as an oil (1.80 g, 8.12 mmol,
4.8. (3-Benzyloxy-2-hydroxy-2-methyl)propyl methane-
sulfonate (R)-10
1
92%). [h]2D5=−3.0 (c 0.8, dichloromethane). H NMR
(CDCl3): l 1.36 (s, 3H, CH3), 1.41 (s, 6H, 2CH3), 3.34
(d, 1H, J=9.0 Hz, CH2), 3.42 (d, 1H, J=9.0 Hz, CH2),
3.70 (d, 1H, J=8.7 Hz, CH2), 4.03 (d, 1H, J=8.7 Hz,
CH2), 4.57 (m, 2H, CH2), 7.34 (m, 5H, Ph). Anal. calcd
for C14H20O3: C, 71.16; H, 8.53. Found: C, 71.61; H,
8.45%. Spectral data were identical to those reported in
the literature (Ref. 23).
To a stirred solution of diol (S)-9 (1.25 g, 6.86 mmol)
and di-iso-propylethylamine (1.07 g, 8.23 mmol) in dry
dichloromethane (30 mL), at 0°C under an inert atmo-
sphere, was added dropwise methanesulfonyl chloride
(0.96 g, 8.23 mmol). The reaction mixture was stirred at
rt for 3 h and saturated aqueous NaHCO3 solution (15
mL) was added. The organic layer was dried (Na2SO4),
concentrated in vacuo and purified by column chro-
matography (hexane/ethyl acetate, 6:4) to give (R)-10
as an oil (1.58 g, 5.76 mmol, 84%). [h]2D5=−2.4 (c 1.07,
Using the method described for its enantiomer (R)-7,
compound (S)-7 (1.82 g, 92%) was obtained from com-
pound (S)-2 (1.30 g, 8.89 mmol). [h]2D5=+2.7 (c 1.05,
dichloromethane). Anal. calcd for C14H20O3: C, 71.16;
H, 8.53. Found: C, 71.92; H, 8.21%.
1
MeOH). H NMR (CDCl3): l 1.24 (s, 3H, CH3), 3.01
(s, 3H, SO2CH3), 3.38 (d, 1H, J=9.3 Hz, CH2), 3.45 (d,
1H, J=9.3 Hz, CH2), 4.12 (d, 1H, J=9.9 Hz, CH2),
4.17 (d, 1H, J=9.9 Hz, CH2), 4.56 (m, 2H, CH2), 7.34
(m, 5H, Ph); 13C NMR (CDCl3): l 21.1 (CH3), 37.2
(SO2CH3), 71.0, 73.0, 73.3, 73.4 (3CH2, C(CH3)OH),
127.7, 127.9, 128.4, 137.4 (Ph). ESI+ (m/z)=275. Anal.
calcd for C12H18O5S: C, 52.54; H, 6.61; S, 11.69.
Found: C, 52.23; H, 6.94; S, 11.12%.
4.6. (2,2,4-Trimethyl-1,3-dioxolane-4-yl)methyl
methanesulfonates (R)-8 and (S)-8
To a stirred solution of alcohol (R)-2 (0.30 g, 2.05
mmol) and di-iso-propylethylamine (0.32 g, 2.46 mmol)

A. A6enoza et al. / Tetrahedron: Asymmetry 12 (2001) 1383–1388
1387
4.9. 2-Benzyloxymethyl-2-methyloxirane (R)-11
sion was filtered to remove N,N%-dicyclohexylurea. The
filtrate was concentrated in vacuo to give a white slurry,
to which ethyl ether (20 mL) was added. The resultant
suspension was filtered to remove the acylurea and the
solvent was evaporated. The residue was purified by
column chromatography (hexane/ethyl acetate, 9.5:0.5)
to give 12 as an oil (99 mg, 0.32 mmol, 52%). [h]2D5=
+29.2 (c 0.33, CHCl3). 1H NMR (CDCl3): l 1.33 (s, 3H,
CH3), 2.66, 2.75 (2d, 2H, J=4.5 Hz, CH2O), 3.56 (s,
3H, CH3O), 4.16, 4.50 (2d, 2H, J=12.0 Hz, CH2OCO),
7.36–7.45 (m, 3H, Ph), 7.48–7.60 (m, 2H, Ph). 13C
NMR (CDCl3): l 18.2 (CH3), 51.9 (CH2O), 54.4
(C(CH3)CH2O), 55.5 (CH3O), 68.8 (CH2OCO), 121.3
(C(CF3)), 125.1 (C(CF3)), 127.3, 128.4, 129.7, 131.9
(Ph), 166.2 (CH2OCO). 19F NMR (CDCl3): l −71.9.
ESI+ (m/z)=305. Anal. calcd for C14H15F3O4: C, 55.26;
H, 4.97. Found: C, 55.07; H, 4.63%.
The mesylate (R)-10 (1.58 g, 5.76 mmol) was dissolved
in dry MeOH (50 mL), which was treated with anhy-
drous K2CO3 (4.02 g, 29.1 mmol). The reaction mixture
was stirred at rt for 4 h. Concentration of the mixture
was followed by dilution with H2O (10 mL) and extrac-
tion with ethyl acetate (30 mL). The separated organic
phase was dried (Na2SO4), concentrated in vacuo and
purified by flash chromatography (hexane/ethyl acetate,
9.5:0.5) to give (R)-11 as an oil (0.81 g, 4.55 mmol,
1
79%). [h]2D5=−10.4 (c 1.26, MeOH). H NMR (CDCl3):
l 1.41 (s, 3H, CH3), 2.64 (d, 1H, J=4.8 Hz, CH2
oxirane), 2.76 (d, 1H, J=4.8 Hz, CH2 oxirane), 3.45 (d,
1H, J=10.8 Hz, CH2OCH2Ph), 3.59 (d, 1H, J=10.8
Hz, CH2OCH2Ph), 4.55 (d, 1H, J=12.0 Hz, CH2Ph),
4.60 (d, 1H, CH2Ph), 7.32 (m, 5H, Ph). Anal. calcd for
C11H14O2: C, 74.13; H, 7.92. Found: C, 74.61; H,
7.45%. Spectral data were identical to those reported in
the literature (Ref. 9a).
Acknowledgements
4.10. 2-Benzyloxymethyl-2-methyloxirane (S)-11
This work was supported by the DGES (project PB97-
0998-C02-02), the Universidad de La Rioja (project
API-00/B02) and Gobierno de La Rioja (doctoral grant
of D. Sucunza).
To a solution of (S)-8 (0.30 g, 1.34 mmol) in THF (5
mL), at rt, aqueous HCl (2N, 5 mL) was added. After
stirring for 2 h, the mixture was extracted with ethyl
acetate (20 mL). The organic phase was dried (Na2SO4)
and concentrated in vacuo to give (S)-(2,3-dihydroxy-2-
methyl)propyl methanesulfonate, which was dissolved
in THF (15 mL) and the mixture was added to NaH
(0.11 g, 2.81 mmol) at 0°C, under an inert atmosphere.
Then, the reaction was warmed to rt and BnBr (0.28 g,
1.60 mmol) and Bu4NI (0.15 g, 0.40 mmol) were added
to the mixture. After stirring for 36 h, the reaction was
quenched by the addition of H2O (10 mL) and
extracted with ethyl acetate (20 mL). The organic phase
was dried (Na2SO4), concentrated in vacuo and purified
by column chromatography (hexane/ethyl acetate,
9.5:0.5) to give (S)-11 as an oil (0.15 g, 0.84 mmol,
63%). [h]2D5=+10.9 (c 1.20, MeOH). Anal. calcd for
C11H14O2: C, 74.13; H, 7.92. Found: C, 74.61; H,
7.45%.
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